Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mol Biol Cell. 2011 Jul 1;22(13):2270-81. doi: 10.1091/mbc.E10-11-0926. Epub 2011 May 11.
Abnormalities in the huntingtin protein (Htt) are associated with Huntington's disease. Despite its importance, the function of Htt is largely unknown. We show that Htt is required for normal chemotaxis and cytokinesis in Dictyostelium discoideum. Cells lacking Htt showed slower migration toward the chemoattractant cAMP and contained lower levels of cortical myosin II, which is likely due to defects in dephosphorylation of myosin II mediated by protein phosphatase 2A (PP2A). htt(-) cells also failed to maintain myosin II in the cortex of the cleavage furrow, generating unseparated daughter cells connected through a thin cytoplasmic bridge. Furthermore, similar to Dictyostelium htt(-) cells, siRNA-mediated knockdown of human HTT also decreased the PP2A activity in HeLa cells. Our data indicate that Htt regulates the phosphorylation status of myosin II during chemotaxis and cytokinesis through PP2A.
亨廷顿病与异常的亨廷顿蛋白（Htt）有关。尽管它很重要，但 Htt 的功能在很大程度上仍是未知的。我们发现 Htt 对于盘基网柄菌中的正常趋化作用和胞质分裂是必需的。缺乏 Htt 的细胞向趋化因子 cAMP 的迁移速度较慢，并且细胞皮层中的肌球蛋白 II 水平较低，这可能是由于蛋白磷酸酶 2A（PP2A）介导的肌球蛋白 II 去磷酸化缺陷所致。htt(-)细胞也无法在分裂沟的皮层中维持肌球蛋白 II，从而产生通过薄细胞质桥连接的未分离的子细胞。此外，与盘基网柄菌 htt(-)细胞类似，siRNA 介导的人 HTT 敲低也降低了 HeLa 细胞中的 PP2A 活性。我们的数据表明，Htt 通过 PP2A 调节趋化作用和胞质分裂过程中肌球蛋白 II 的磷酸化状态。
